Grove Instruments (formerly VivaScan) intends to promote the benefits of good glycemic control by bringing to market a completely noninvasive, bloodless, and painless glucometer that allows all people with diabetes to test their blood sugar optimally and thus improve their glycemic control. Grove Instrument's noninvasive blood glucometer is based on measurements of near-infrared (NIR) light absorption in blood. Our technology utilizes a patented Optical Bridge" (OB) method, an optical equivalent of the well-known electrical Wheatstone bridge. SBIR grant and company funds have enabled Grove Instruments to develop and successfully test an advanced laboratory prototype handheld noninvasive blood glucometer. Currently, our patient device must be calibrated with a blood-based glucometer prior to use during a three to four hour measurement session. Our objective is to test the feasibility of developing a universal calibration method which will allow the user to employ our noninvasive glucometer without a pre-use calibration session, similar to pulse oximetry. Currently, we use a partial least squares regression to develop individual models for each subject. The proposed new universal model uses a classification method based upon principal component analysis with a simulated annealing and a Metropolis algorithm. A pilot study showed a reduction in the average error by 15% for the universal model vs. the individual blood calibration model. Specific Aims for the proposed project include: 1) Collect measurement data from a cohort of demographically-diverse diabetic in order to provide a training set for the proposed Universal Calibration Model, 2) Develop a test bench for the universal calibration model in MATLAB and test various improvements in potential universal models using the data collected, 3) Port the optimized MATLAB model into C++ in order to enable real-time operation, 4) Recruit a large and demographically balanced cohort of diabetic subjects for clinical testing in order to verify the proposed method works on at 90% or better of the subjects in the study, regardless of age, gender, or racial/ethnic background, and 5) Write final report for Phase I. Phase II work will develop and test a compact, affordable noninvasive glucometer. The proposed device has dramatic implications for the quality of glucose control for diabetic persons and their quality of life and longevity. Optimizing glucose testing with the Grove Instruments device can lead to improved clinical outcomes and substantial cost savings to the individual patient and to the entire health care system, and the existence of a universally calibrated device would provide substantial opportunity to obtain better glycemic control on the widest possible segment of the population.